FIGURE 1: Three-dimensional view of the Rubella virus molecule.
DISEASE/DRUG OF INTEREST:Measles MOTIVATION AND BACKGROUND:Measles, otherwise known as Red Measles or Rubella, is a contagious disease caused by a virus of the genus Morbilivirus. This virus directly affects the respiratory system and grows in the epithelial cells lining the back of the throat and lungs. It spreads when an infected person coughs, sneezes or shares food and/or drinks with other unprotected individuals. One can also contract this disease through the air, just by being near an infected individual. Consequently, they can spread this highly transmittable disease to others before experiencing any noticeable symptoms in the phenotype. Historically, before widespread vaccination was available worldwide, measles was a very common disease that almost every child was expected to procure at some point by the age of 20. Today however, in developed countries such as the United States and Canada measles is very rare because citizens are kept vaccinated. The few cases still reported annually mostly originate outside of the country. Such random breakouts due to travelers that visit from foreign countries who were infected with the disease before or during their trip and then brought the contagion to unvaccinated individuals. Since children in developed countries get the measles vaccine as a part of their regular shots they are not susceptible to the disease. Once they have received the immunization individuals are immune to the disease for the entirety of their lives. On the other hand, in today’s world the most vulnerable of the human population to catching this virus live in undeveloped countries. In these regions the population does not have easy access to vaccinations because of poor health care systems and lacking financial economies to pay for such luxuries. If an individual is infected with this disease many symptoms may come along with it that affect the individual's general health. These include:
FIGURE 2: Symptomatic rash caused by Measles. This case is very extreme but it gives a good idea of just how severe the side effects of this disease can be. Flat discolored areas called macules appear first, follow then by solid, red raised areas referred to as papules.
fever
runny nose
hacking cough
rash all over the body
This rash may last from 4 to 7 days, starting on the head and spreading down the body, appearing as flat discolored areas called macules and then as solid, red raised areas referred to as papules. Once diagnosed, present-day patients are normally treated with home care, medicine to lower fevers such as Tylenol, lots of rest, fluids and caution to stay away from other people. Most people today get better within two weeks but there are still some possible complications that can come along with this disease such as lung infection (Pneumonia), brain swelling (Encephalitis) or in very rare cases Meningitis or seizures. Overall, despite the current levels of vaccination in most countries and impressive improvements over the past decades in preventing this disease there are still an estimated 164,000 people yearly that are killed by Malaria.
TARGET INFORMATION:
Recent studies have shown that surfacing of new information about the structure of the protein the virus uses to attach itself to its target cells could offer a fresh tactic to fight contagion. The molecule known as Measles Virus Hemagglutinin, orMVH, is what drug-designers will need to consider when they are trying to hinder further contamination by getting in the way of the virus’ grip on its host cell. MVH is a glycol-protein anchored to the virus envelope that initiates infection when it is attached to the host cell receptors. Researchers have utilized x-ray crystallography to solve the composition of MVH. From this technique it was deduced that the structure of MVH is to be shaped like a propeller with its ‘blades’ radiating out in such a way that they can attach to the host cell during the course of infection. There is a similar protein called Neuraminidase, also with a propeller shape that employs a cleft at the middle of the propeller to join carbohydrates on the cells that they taint. A feature that makes the measles virus distinctively different is its capability to unite two non-overlapping host cell receptors referred to as SLAM and CD46. In other words, it does not use carbohydrates to unite to host cells.
FIGURE 3: Structure of the MVH protein. In this case it is bound to the CD46 receptor.
FIGURE 4: The unique, elongated groove in MVH mediates receptor recognition of SLAM and CD46.
DRUG INFORMATION:
Today, the most common way of preventing Measles is the vaccine called Mumps-Rubella-Varicella combo (MMRV). If one has already been an infected there is no cure, only a common medicine like Tylenol can help to reduce the side effects of this disease. MMRV includes small doses of living but inactivated viruses that cause measles, mumps and rubella acting to provoke the natural immune system’s reaction. In the end, the effect of this vaccine is life-long, working successfully to thwart any potential risk of contamination in human individuals. The delivery method of this drug is through an injection of the skin on the upper arm area, with doses varying slightly depending on age. There are minor side effects associated with this injection such as:
fever
pain at shot site
headache
most typical symptom: rash
Some parents will not allow their children to receive the vaccination because of the fear that it can cause autism, however studies have shown no connection between these two. The continued practice of parents depriving their children of MMRV can potentially lead to an outbreak in the future; if they go around without vaccination and come in contact with the illness they will inevitably spread it to others who are also unprotected. Different versions of this vaccine have been patented and sold by varying companies in different countries, each name differing depending on which maker it is bought from. Studies on animals have shown adverse effects but adequate studies on humans are not available. There are, however, 13 open clinical trials studying this disease and vaccine taking place currently. Alternatives to this vaccine include another injection called ProQuad which aims to protect against the same diseases and symptoms as MMRV. Both of these vaccines treat multiple conditions including mumps, measles, rubella and varicella. It is very rare nowadays for a measle-only vaccine to be administered.
REFERENCES:
1. Global control and regional elimination of measles, 2000–2012. Wkly Epidemiol Rec2014, 89 (6), 45-52. 2.C. Santiago, M. Celma, T. Stehle, J. Casasnovas. Structure of the Measles Virus Hemagglutinin Bound to the CD46 Receptor. Nature Structure and Molecular Biology 2010, 17, (1), 124-129 3.C. Navaratnarajah, N. Oezguen, L. Rupp, L. Kay, V. Leonard, W. Braun, R. Cattaneo. The Heads of the Measles Virus Attachment Protein Move to Transmit the Fusion-triggering Signal. Nature Structure and Molecular Biology 2011, 18, (2), 128-134.
MOTIVATION AND BACKGROUND:Measles, otherwise known as Red Measles or Rubella, is a contagious disease caused by a virus of the genus Morbilivirus. This virus directly affects the respiratory system and grows in the epithelial cells lining the back of the throat and lungs. It spreads when an infected person coughs, sneezes or shares food and/or drinks with other unprotected individuals. One can also contract this disease through the air, just by being near an infected individual. Consequently, they can spread this highly transmittable disease to others before experiencing any noticeable symptoms in the phenotype.
Historically, before widespread vaccination was available worldwide, measles was a very common disease that almost every child was expected to procure at some point by the age of 20. Today however, in developed countries such as the United States and Canada measles is very rare because citizens are kept vaccinated. The few cases still reported annually mostly originate outside of the country. Such random breakouts due to travelers that visit from foreign countries who were infected with the disease before or during their trip and then brought the contagion to unvaccinated individuals. Since children in developed countries get the measles vaccine as a part of their regular shots they are not susceptible to the disease. Once they have received the immunization individuals are immune to the disease for the entirety of their lives. On the other hand, in today’s world the most vulnerable of the human population to catching this virus live in undeveloped countries. In these regions the population does not have easy access to vaccinations because of poor health care systems and lacking financial economies to pay for such luxuries.
If an individual is infected with this disease many symptoms may come along with it that affect the individual's general health. These include:
FIGURE 2: Symptomatic rash caused by Measles. This case is very extreme but it gives a good idea of just how severe the side effects of this disease can be. Flat discolored areas called macules appear first, follow then by solid, red raised areas referred to as papules.
fever- runny nose
- hacking cough
- rash all over the body
This rash may last from 4 to 7 days, starting on the head and spreading down the body, appearing as flat discolored areas called macules and then as solid, red raised areas referred to as papules. Once diagnosed, present-day patients are normally treated with home care, medicine to lower fevers such as Tylenol, lots of rest, fluids and caution to stay away from other people. Most people today get better within two weeks but there are still some possible complications that can come along with this disease such as lung infection (Pneumonia), brain swelling (Encephalitis) or in very rare cases Meningitis or seizures. Overall, despite the current levels of vaccination in most countries and impressive improvements over the past decades in preventing this disease there are still an estimated 164,000 people yearly that are killed by Malaria.TARGET INFORMATION:
Recent studies have shown that surfacing of new information about the structure of the protein the virus uses to attach itself to its target cells could offer a fresh tactic to fight contagion. The molecule known as Measles Virus Hemagglutinin, or MVH, is what drug-designers will need to consider when they are trying to hinder further contamination by getting in the way of the virus’ grip on its host cell. MVH is a glycol-protein anchored to the virus envelope that initiates infection when it is attached to the host cell receptors. Researchers have utilized x-ray crystallography to solve the composition of MVH. From this technique it was deduced that the structure of MVH is to be shaped like a propeller with its ‘blades’ radiating out in such a way that they can attach to the host cell during the course of infection. There is a similar protein called Neuraminidase, also with a propeller shape that employs a cleft at the middle of the propeller to join carbohydrates on the cells that they taint. A feature that makes the measles virus distinctively different is its capability to unite two non-overlapping host cell receptors referred to as SLAM and CD46. In other words, it does not use carbohydrates to unite to host cells.DRUG INFORMATION:
Today, the most common way of preventing Measles is the vaccine called Mumps-Rubella-Varicella combo (MMRV). If one has already been an infected there is no cure, only a common medicine like Tylenol can help to reduce the side effects of this disease. MMRV includes small doses of living but inactivated viruses that cause measles, mumps and rubella acting to provoke the natural immune system’s reaction. In the end, the effect of this vaccine is life-long, working successfully to thwart any potential risk of contamination in human individuals.The delivery method of this drug is through an injection of the skin on the upper arm area, with doses varying slightly depending on age.
There are minor side effects associated with this injection such as:
- fever
- pain at shot site
- headache
- most typical symptom: rash
Some parents will not allow their children to receive the vaccination because of the fear that it can cause autism, however studies have shown no connection between these two. The continued practice of parents depriving their children of MMRV can potentially lead to an outbreak in the future; if they go around without vaccination and come in contact with the illness they will inevitably spread it to others who are also unprotected.Different versions of this vaccine have been patented and sold by varying companies in different countries, each name differing depending on which maker it is bought from. Studies on animals have shown adverse effects but adequate studies on humans are not available. There are, however, 13 open clinical trials studying this disease and vaccine taking place currently. Alternatives to this vaccine include another injection called ProQuad which aims to protect against the same diseases and symptoms as MMRV. Both of these vaccines treat multiple conditions including mumps, measles, rubella and varicella. It is very rare nowadays for a measle-only vaccine to be administered.
REFERENCES:
1. Global control and regional elimination of measles, 2000–2012. Wkly Epidemiol Rec2014, 89 (6), 45-52.2.C. Santiago, M. Celma, T. Stehle, J. Casasnovas. Structure of the Measles Virus Hemagglutinin Bound to the CD46 Receptor. Nature Structure and Molecular Biology 2010, 17, (1), 124-129
3.C. Navaratnarajah, N. Oezguen, L. Rupp, L. Kay, V. Leonard, W. Braun, R. Cattaneo. The Heads of the Measles Virus Attachment Protein Move to Transmit the Fusion-triggering Signal. Nature Structure and Molecular Biology 2011, 18, (2), 128-134.
EXTERNAL LINKS:
Measles.http://www.nlm.nih.gov/medlineplus/ency/article/001569.htm (accessed 2/3/14), part of NIH. http://www.nlm.nih.gov/ (accessed 2/3/14).
C. Garcia. Measles Structure OffersDrug Design Guide.http://www.hhmi.org/news/measles-structure-offers-drug-design-guide(accessed 12/15/03), part of Howard Hughes Medical Institute. http://www.hhmi.org/ (accessed 12/15/03).
Overview of Measles Disease.http://www.cdc.gov/measles/about/overview.html(accessed 12/15/03), part of Centers for Disease Control and Prevention. http://www.cdc.gov/ (accessed 12/15/03).